Neurotrophic and immunomodulatory lanostane triterpenoids from wood-inhabiting Basidiomycota

Abstract

AbstractNeurotrophins such as nerve growth factor (ngf) and brain derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for treatment of neurodegerative diseases including Alzheimer’s disease and Parkinson’s disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from fruiting bodies ofLaetiporus sulphureusand a mycelial culture ofAntrodiasp. MUCL 56049. The structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution Electrospray mass spectrometry (HR-ESIMS). The secondary metabolites were tested for neurotrophin (ngfandbdnf) expression levels on human astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the expression of neurotrophic factors namely,ngf(sulphurenic acid, 15α-dehydroxytrametenolic acid, fomefficinic acid D and 16α-hydroxyeburicoic acid) andbdnf(sulphurenic acid and 15α- dehydroxytrametenolic acid), respectively. The triterpenes also potentiatedngf-induced neurite outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound class of lanostanes in direct relation tobdnfandngfenhancement. These compounds are widespread in medicinal mushrooms; hence, they appear promising as starting point for development of drugs and mycopharmaceuticals to combat neurodegenerative diseases. Interestingly, they do not show any pronounced cytotoxicity and may therefore be better suited for therapy than many other neurotrophic compounds that were previously reported.